InCl3-SiO2 catalyzed electrophilic amination of arenes: A facile and rapid synthesis of aryl hydrazides

Article abstract of DOI:10.1055/s-2001-18075

Electron-rich arenes undergo electrophilic amination with diethyl azodicarboxylate on the surface of silica gel impregnated with indium trichloride in solvent-free conditions to afford parasubstituted aryl hydrazides. Improved yields and enhanced rates are obtained by employing microwave irradiation.

Full text of DOI:10.1055/s-2001-18075

LETTER
1781
InCl3-SiO2 Catalyzed Electrophilic Amination of Arenes: A Facile and Rapid
Synthesis of Aryl Hydrazides1
I
.
c
atalyzedel
S
ectrophilic am
.
ination of ar
Y
e
nes adav,* B. V. Subba Reddy, G. Mahesh Kumar, C. Madan
3
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Fax +91(40)7170512; E-mail: yadav@iict.ap.nic.in
Received 30 May 2001
thesis of aryl hydrazides through the electrophilic amina-
Abstract: Electron-rich arenes undergo electrophilic amination
with diethyl azodicarboxylate on the surface of silica gel impregnat-
ed with indium trichloride in solvent-free conditions to afford para-
substituted aryl hydrazides. Improved yields and enhanced rates are
obtained by employing microwave irradiation.
tion of electron rich arenes with diethyl azodicarboxylate
11
using indium trichloride supported on SiO2 in solvent-
free conditions.
Key words: InCl3-SiO2, arenes, aryl hydrazides, microwaves.
Scheme
Aryl hydrazides are versatile intermediates for the synthe-
sis of aromatic amines2 and aryl hydrazines.3 Aromatic
amines exhibit a wide spectrum of biological activities4
such as antibiotics, analgesics and -adrenergic blockers.
In addition, aromatic amines are the key intermediates for
the synthesis of a variety of aromatic compounds via dia-
zotization and nucleophilic substitution reactions. Aryl
hydrazines are important precursors for the synthesis of a
variety of heterocycles5 such as indoles, pyrazoles, -lac-
tams, quinazolines and many others, which are known to
be biologically active. Aryl hydrazides can be prepared by
the condensation of aryl lithium or aryl magnesium re-
agents with di-t-butyl azodicarboxylate6 and also by the
electrophilic amination of electron-rich arenes with
bis(2,2,2-trichloroethyl)azodicarboxylate under thermal
or Lewis acid catalysis.7,8 A thermal or acid catalyzed
electrophilic amination typically requires high tempera-
ture or strongly acidic conditions and the highly reactive
bis(trichloroethyl)azodicarboxylate to promote the ami-
nation reaction. Further, many of these procedures are of
limited synthetic scope due to lower yields, poor regiose-
lectivity, extended reaction time, high temperature and the
amount of the catalyst or solvent used. However, there is
no report on the synthesis of aryl hydrazides from arenes
and diethyl azodicarboxylate using indium halides. There-
fore, the development of new methods that lead to conve-
nient procedures and better yields are of interest. In recent
years, there has been increasing interest on solid support-
ed reagents coupled with microwave irradiation9 due to
the benefits of enhanced reaction rates, improved yields,
cleaner reaction profiles, greater selectivity and opera-
tional simplicity.
Aryl hydrazides were formed in high yields in a short re-
action time when the reactants were admixed with InCl3-
SiO2 in Erlenmeyer flask and exposed to microwave irra-
diation at 450 W using BPL, BMO-700 T focused micro-
wave oven (Scheme). The reactions were clean and
completed in 2-6 min with high regioselectivity. The less
reactive substrates like anisole, naphthalene, 3,4-
dimethoxybromobenzene, 1,4-dimethoxybenzene and xy-
lene smoothly underwent electrophilic amination to af-
ford corresponding hydrazides in good yields under
microwave irradiation. The electrophilic amination reac-
tion of arenes with diethyl azodicarboxylate in the pres-
ence of BF3 OEt2 or CF3SO3H, or TFA resulted in a
complex mixture of products and also the amination was
much slower using LiClO4 as a catalyst compared to reac-
tions carried out in the presence of indium trichloride-
SiO2 under microwave irradiation. The reaction rates and
yields were dramatically enhanced by microwave irradia-
tion. This is due to the more absorption of microwave en-
ergy by the polar media as well as polar reactants, which
generates heat energy as required to promote the amina-
tion reaction. The reaction is highly regioselective, afford-
ing high yields of products in a short reaction time.
The present study has unequivocally confirmed that the
conventional heating in 1,2-dichloroethane and longer re-
action times (8-22 h) required for the amination of arenes
are improved using microwave irradiation, which is be-
coming an alternate and substitute heating source. For ex-
ample, the treatment of 1,2-dimethoxybenzene with
diethyl azodicarboxylate in the presence of indium
trichloride-SiO2 (3 wt equiv of arene) under microwave ir-
radiation at 450 watts for 3 min gave the corresponding
hydrazide in 88% yield after filtration through a small sil-
ica gel column, whereas under conventional heating con-
ditions, the hydrazide was obtained in 75% yield after 10
h of heating in 1,2-dichloroethane12 (Table, entry, a). In-
variably, the products obtained by microwave irradiation
were purified with more ease. The hydrazides thus ob-
In continuation of our interest on surface mediated solid
state reactions coupled with microwave irradiation,10
herein we report an efficient and rapid method for the syn-
Synlett 2001, No. 11, 26 10 2001. Article Identifier:
1437-2096,E;2001,0,11,1781,1783,ftx,en;D13301ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1782
J. S. Yadav et al.
LETTER
Table Indium(III)Chloride-SiO2 Catalyzed Electrophilic Amination of Arenes with DEAD.
Entry
a
Arene
Hydrazidea
Microwaveb
Time (Yield)
Conventional Heatingc
Time (Yield)
3 min (88)
10 h (75)
b
2 min (92)
8 h (80)
c
3 min (87)
3 min (81)
12 h (70)
15 h (68)
d
e
f
3 min (85)
2 min (90)
10 h (73)
8 h (78)
g
h
6 min (83)
3 min (87)
14 h (71)
12 h (78)
i
j
3 min (90)
4 min (72)
12 h (78)
20 h (65)
k
l
6 min (78)
6 min (75)
22 h (62)
15 h (71)
m
6 min (68)
22 h (60)
a All products were characterized by 1H NMR, IR and Mass spectra.12,
b Microwave irradiation was carried out at 450 W (BPL, BMO 700 T).
c Conventional heating in 1,2-dichloroethane.
tained were easily converted to their corresponding silica gel in solvent-free conditions. The procedure offers
anilines by reducing with zinc in acetic acid.
several advantages including mild reaction conditions,
cleaner reaction profiles, high regioselectivity, short reac-
tion times, high yields of aminated products and simple
experimental / product isolation procedures which makes
it a useful and attractive alternative process for acid sensi-
tive molecules where nitration conditions are unsuitable.
In conclusion, the method describes a rapid and efficient
procedure for the preparation of aryl hydrazides through
the electrophilic amination of arenes with diethyl azodi-
carboxylate catalyzed by indium trichloride supported on
Synlett 2001, No. 11, 1781–1783 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
InCl3-SiO2 catalyzed electrophilic amination of arenes
1783
(10) (a) Sampath Kumar, H. M.; Subba Reddy, B. V.; Jagan
Reddy, E.; Yadav, J. S. Green Chemistry 1999, 141.
(b) Sampath Kumar, H. M.; Subba Reddy, B. V.; Yadav, J.
S. Chemistry Lett. 1998, 637. (c) Sampath Kumar, H. M.;
Subba Reddy, B. V.; Jagan Reddy, E.; Yadav, J. S.
Tetrahedron Lett. 1999, 40, 2401.
(11) The catalyst (InCl3-SiO2) was prepared by adding silica gel
(2 g , Aldrich, 230-400 mesh) to a stirred solution of InCl3
(0.3 mmol) in acetonitirle (2 mL) followed by evaporation of
solvent in vacuo.
Acknowledgement
BVS and GMK thank CSIR, New Delhi for the award of fel-
lowships.
References and Notes
(1) IICT Communication number: 4574.
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(12) (a) Microwave irradiation: 1,2-Dimethoxybenzene (5
mmol), diethyl azodicarboxylate (5 mmol) and InCl3-SiO2 (3
wt equiv of arene) were admixed in Erlenmeyer flask and
exposed to microwave irradiation at 450 watts using BPL,
BMO-700 T focused microwave oven for 3 min (pulsed
irradiation 1 min with 20 s interval). On completion, the
reaction mixture was directly charged on a small silica gel
column and eluted with a mixture of ethyl acetate–hexane
(2:8)to afford pure hydrazide in 88% yield as a pale yellow
solid. (b) Conventional method: A mixture of 1,2-dimethoxy
benzene (5 mmol), DEAD (5 mmol) and InCl3 (10 mol%) in
1,2- dichloroethane (10 mL) was stirred at reflux for 10 h.
On completion, the reaction mass was diluted with H2Oand
extracted with CHCl3 (2 15 mL). The organic layers were
dried over anhydrous Na2SO4 and purified by column
chromatography to afford pure hydrazide in 75% yield as
pale yellow solid. mp 108-110 °C, IR(KBr): 3280, 2990,
1741, 1709, 1529, 1248, 1023 cm-1. 1H NMR (CDCl3) : 1.25
(t, 6 H, J = 6.8 Hz), 3.80 (s, 6 H), 4.20 (q, 4 H, J = 6.8 Hz),
6.80 (d, 1 H, J = 8.0 Hz), 6.9 (dd, 1 H, J = 8.0 and 2.4 Hz),
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z)(%): 312(80)M+, 240(50), 225(30), 179(10), 167(100),
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Synlett 2001, No. 11, 1781–1783 ISSN 0936-5214 © Thieme Stuttgart · New York